Clinical profile and management outcomes of posterior zone 1 retinopathy of prematurity.

BACKGROUND: To analyse the varied clinical profile and treatment outcomes of posterior zone 1 retinopathy of prematurity (ROP). METHODS: This retrospective case-series included 54 eyes of 27 infants of posterior zone 1 ROP treated at our centre from January 2018 to June 2019. Three clinical patterns were observed at presentation - Posterior zone 1 ROP without detachment (group 1), with subtotal detachment (group 2) and total detachment (group 3) of the vascularised retina. Their profile, treatment options and outcomes were studied. RESULTS: The mean birth weight was 1204 ± 262 gm and mean gestational age was 28.8 ± 2 weeks. Clinical presentation as per group 1, 2 and 3 was seen in 33/54 (61.1%), 9/54 (16.6%) and 12/54 (22.2%) eyes, respectively. All the eyes received intravitreal ranibizumab as primary intervention. In group 1, 25/33 (75.7%) eyes had laser and 8/33 (24.2%) had surgery whereas, in group 2, 2/9 (22.2%) eyes had laser and 7/9 (77.7%) underwent surgery as a second intervention. In group 3, only 3 /12 (25%) eyes had second intervention (surgery). Surgical outcomes of group 1 and 2 were better than group 3. At last follow-up, macular vascularisation was noted in 33/54 (61.1%) eyes. CONCLUSION: A customised and multifaceted treatment approach is required to treat posterior zone 1 ROP.

Low dose fentanyl infusion versus 24% oral sucrose for pain management during laser treatment for retinopathy of prematurity-an open label randomized clinical trial.

To compare the efficacy of low dose fentanyl infusion and 24% oral sucrose in providing optimal pain relief during laser for retinopathy of prematurity (ROP), we enrolled fifty-eight spontaneously breathing preterm infants undergoing laser. The preterm infants were randomized to either fentanyl infusion (1 mcg/kg/hr) or 24% oral sucrose (2 ml). We evaluated and compared the proportion of time spent crying during the procedure, salivary cortisol before and after the procedure, premature infant pain profile- revised (PIPP-R) scores during the procedure, apnoea during and after the procedure, need for mechanical ventilation, and feed intolerance and urinary retention 24 h after the procedure between the two groups. We found that the proportion of time spent crying during the procedure was significantly less in the fentanyl group [62.5% (50.7-74.2) vs 73.8% (55.6-83.4); P = 0.02]. Average PIPP-R score during the procedure was significantly less in the fentanyl group [7.2 vs 9.0; (mean difference of - 1.8; P = 0.01)]. There was no difference in other outcomes between the two groups.Conclusion: During laser for ROP, low dose fentanyl infusion was found to be efficacious in reducing pain as compared with 24% sucrose.What is Known:• Preterm infants undergoing laser photocoagulation for ROP suffer significant amount of pain.• Standard of care for pain relief in infants undergoing laser therapy in developed countries is general anesthesia (GA) or combination of sedation, analgesia, and paralysis (SAP).What is New:• During laser photocoagulation for ROP, fentanyl infusion at low dose (1 mcg/kg/hr) is efficacious in reducing pain as compared to 24% oral sucrose.

ATYPICAL MACULAR HOLES.

PURPOSE: To study the etiology, clinical features, management options, and visual prognosis in various types of atypical macular holes (MHs). METHODS: A review of the literature was performed, which focused on the etiopathogenesis of atypical or secondary MHs, their differentiating clinical features, management strategies, and varied clinical outcomes. Idiopathic or age-related, myopic, and traumatic MHs were excluded. RESULTS: Atypical or secondary MHs arise out of concurrent ocular pathologies (dystrophy, degeneration, or infections) and laser/surgery. The contributing factors may be similar to those responsible for idiopathic or typical MHs, i.e., tangential or anteroposterior vitreofoveal traction or cystoid degeneration. The management is either observation or treatment of the underlying cause. The prognosis depends on the background pathology, duration of disease, and baseline visual acuity governed by the size of MH and morphologic health of underlying RPE and photoreceptors. The closer the morphology of atypical MH is to that of an idiopathic MH, the better the surgical outcome is. CONCLUSION: With the advancements in retinal imaging, atypical MHs are now more frequently recognized. With increasing understanding of the underlying disease processes, and improvement in investigations and surgical treatment, management of atypical MHs may improve in the future.

Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis in foetal life. Researchers have recently attempted to use anti-VEGF agents for the treatment of retinopathy of prematurity (ROP), a vasoproliferative disorder. The safety and efficacy of these agents in preterm infants with ROP is currently uncertain. OBJECTIVES: To evaluate the efficacy and safety of anti-VEGF drugs when used either as monotherapy, that is without concomitant cryotherapy or laser therapy, or in combination with planned cryo/laser therapy in preterm infants with type 1 ROP (defined as zone I any stage with plus disease, zone I stage 3 with or without plus disease, or zone II stage 2 or 3 with plus disease). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11), MEDLINE (1966 to 11 December 2016), Embase (1980 to 11 December 2016), CINAHL (1982 to 11 December 2016), and conference proceedings. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that evaluated the efficacy or safety of administration, or both, of anti-VEGF agents compared with conventional therapy in preterm infants with ROP. DATA COLLECTION AND ANALYSIS: We used standard Cochrane and Cochrane Neonatal methods for data collection and analysis. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: Six trials involving a total of 383 infants fulfilled the inclusion criteria. Five trials compared intravitreal bevacizumab (n = 4) or ranibizumab (n = 1) with conventional laser therapy (monotherapy), while the sixth study compared intravitreal pegaptanib plus conventional laser therapy with laser/cryotherapy (combination therapy).When used as monotherapy, bevacizumab/ranibizumab did not reduce the risk of complete or partial retinal detachment (3 studies; 272 infants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.21 to 5.13; risk difference (RD) 0.00, 95% CI -0.04 to 0.04; very low-quality evidence), mortality before discharge (2 studies; 229 infants; RR 1.50, 95% CI 0.26 to 8.75), corneal opacity requiring corneal transplant (1 study; 286 eyes; RR 0.34, 95% CI 0.01 to 8.26), or lens opacity requiring cataract removal (3 studies; 544 eyes; RR 0.15, 95% CI 0.01 to 2.79). The risk of recurrence of ROP requiring retreatment also did not differ between groups (2 studies; 193 infants; RR 0.88, 95% CI 0.47 to 1.63; RD -0.02, 95% CI -0.12 to 0.07; very low-quality evidence). Subgroup analysis showed a significant reduction in the risk of recurrence in infants with zone I ROP (RR 0.15, 95% CI 0.04 to 0.62), but an increased risk of recurrence in infants with zone II ROP (RR 2.53, 95% CI 1.01 to 6.32). Pooled analysis of studies that reported eye-level outcomes also revealed significant increase in the risk of recurrence of ROP in the eyes that received bevacizumab (RR 5.36, 95% CI 1.22 to 23.50; RD 0.10, 95% CI 0.03 to 0.17). Infants who received intravitreal bevacizumab had a significantly lower risk of refractive errors (very high myopia) at 30 months of age (1 study; 211 eyes; RR 0.06, 95% CI 0.02 to 0.20; RD -0.40, 95% CI -0.50 to -0.30; low-quality evidence).When used in combination with laser therapy, intravitreal pegaptanib was found to reduce the risk of retinal detachment when compared to laser/cryotherapy alone (152 eyes; RR 0.26, 95% CI 0.12 to 0.55; RD -0.29, 95% CI -0.42 to -0.16; low-quality evidence). The incidence of recurrence of ROP by 55 weeks' postmenstrual age was also lower in the pegaptanib + laser therapy group (76 infants; RR 0.29, 95% CI 0.12 to 0.7; RD -0.35, 95% CI -0.55 to -0.16; low-quality evidence). There was no difference in the risk of perioperative retinal haemorrhages between the two groups (152 eyes; RR 0.62, 95% CI 0.24 to 1.56; RD -0.05, 95% CI -0.16 to 0.05; very low-quality evidence). However, the risk of delayed systemic adverse effects with any of the three anti-VEGF drugs is not known. AUTHORS' CONCLUSIONS: Implications for practice: Intravitreal bevacizumab/ranibizumab, when used as monotherapy, reduces the risk of refractive errors during childhood but does not reduce the risk of retinal detachment or recurrence of ROP in infants with type 1 ROP. While the intervention might reduce the risk of recurrence of ROP in infants with zone I ROP, it can potentially result in higher risk of recurrence requiring retreatment in those with zone II ROP. Intravitreal pegaptanib, when used in conjunction with laser therapy, reduces the risk of retinal detachment as well as the recurrence of ROP in infants with type 1 ROP. However, the quality of the evidence was very low to low for most outcomes due to risk of detection bias and other biases. The effects on other critical outcomes and, more importantly, the long-term systemic adverse effects of the drugs are not known. Insufficient data precludes strong conclusions favouring routine use of intravitreal anti-VEGF agents - either as monotherapy or in conjunction with laser therapy - in preterm infants with type 1 ROP. IMPLICATIONS FOR RESEARCH: Further studies are needed to evaluate the effect of anti-VEGF agents on structural and functional outcomes in childhood and delayed systemic effects including adverse neurodevelopmental outcomes.

TWENTY-FIVE-GAUGE PARS PLANA VITRECTOMY IN COMPLEX RETINAL DETACHMENTS ASSOCIATED WITH GIANT RETINAL TEAR.

PURPOSE: To study the structural and functional outcomes of 25-gauge pars plana vitrectomy in giant retinal tear-associated retinal detachments. METHODS: Seventeen eyes of 17 patients with giant retinal tear, who underwent 25-gauge pars plana vitrectomy over a period of 15 months at a tertiary eye care center by a single surgeon, were recruited in this retrospective interventional study. RESULTS: Giant retinal tears were mostly traumatic (35.3%) or associated with myopia (35.3%) and occurred in young (mean age 25.7 years) males (94.1%). Most eyes had best-corrected visual acuity ≤20/1,200 (in 82.3%), foveal detachment (in 88.2%), and proliferative vitreoretinopathy ≤Grade B (in 82.3%). The giant retinal tear extent was more than 180° in 29.4% and the fellow eye was involved in 35.2% of eyes. All eyes underwent 25-gauge pars plana vitrectomy with encircling band in 41.1%, perfluorocarbon liquid use in 82.3%, and endotamponade with sulphur hexafluoride (23.6%) or silicone oil (76.4%). At mean follow-up of 10.2 months, reattachment rate was 88.2%. Only 35.2% of eyes achieved final visual acuity ≥20/80 with a cause of poor vision being cataract, secondary glaucoma, macular pucker, and corneal edema. CONCLUSION: Twenty-five-gauge pars plana vitrectomy can achieve excellent attachment rates in eyes with giant retinal tear-associated retinal detachment. It can be as efficient as larger-gauge vitrectomy, at the same time retaining all advantages of smaller-gauge surgery.

Retinal Macroaneurysm Associated with Congenital Anomalous Retinal Artery.

PURPOSE: Retinal arteriolar macroaneurysms are a common cause of vision loss in elderly patients with hypertension and cardiovascular disease. Their occurrence in the young, however, is not well known. The purpose of this article is to describe an unusual cause of retinal arteriolar macroaneurysm in a healthy young man. CASE REPORT: A 30-year-old man presented with preretinal hemorrhage and macular exudation due to ruptured retinal artery macroaneurysm. The patient was treated with intravitreal bevacizumab and laser photocoagulation to the macroaneurysm. The exudation and preretinal hemorrhage resolved over several months. Fluorescein angiogram at this stage revealed a congenital anomalous retinal artery. CONCLUSIONS: Congenital anomalous retinal artery may be associated with retinal artery macroaneurysm even in the young age in the absence of any other predisposing factors. The presentation and treatment of such retinal artery macroaneurysm, however, may remain the same to those that occur in older patients.

Pharmacological Interventions for Vascular Targeting in Retinopathy of Prematurity: An Experimental Study.

Purpose: This study was conducted to evaluate the pharmacological interventions to target vascular proliferation in the Retinopathy of Prematurity (ROP). Methods: Protein Kinase C modulator (Bryostatin), tubulin polymerization inhibitor (Dolastatin 10), antiVEGF (Bevacizumab) and a non-specific VEGF inhibitor (Thalidomide) were screened in Retinopathy of Prematurity (ROP) model. The retinal vasculature was evaluated by calculating the tortuosity indices of vessels and electroretinography responses in terms of 'b' wave amplitude and was recorded from ROP rats on postnatal Day 17 and Day 25. Results: Retinopathy was seen in the form of tortousity of vessels at the posterior pole with arteries being affected more than veins. Maximum reduction in tortousity of vessels and the highest 'b' wave amplitude noted in bryostatin with a significant correlation between the two. Conclusion: Bryostatin showed a potential anti-angiogenic effect on the progression of ROP and may hold a promising future in the treatment of ROP.

Clinical Profile, Antibiotic Resistance and Outcomes in Bacterial Endophthalmitis: Coagulase-Negative Staphylococcus Endophthalmitis as Compared to Other Organisms.

BACKGROUND: To evaluate the clinical profile, outcomes and antibiotic resistance in bacterial endophthalmitis. METHODS: This was a post-hoc analysis of a study conducted at a tertiary centre, where 60 consecutive cases of culture-proven bacterial endophthalmitis were included prospectively. Group 1 included coagulase-negative Staphylococcus endophthalmitis (CNSE), while group 2 included the remaining cases. Clinical features, antibiotic resistance and visual outcomes were compared. Visual acuity >3/60 at six months of follow-up was defined as a good visual outcome. RESULTS: Group 1 had 31 cases, while group 2 had 29. Group 2 included 12 gram-positive and 17 gram-negative isolates. Among the groups, group 2 had more patients with presenting visual acuity below hand motions close to the face (25 vs. 12, p<0.001), poor visual outcomes (26 vs. 3, p<0.001) and retinal detachment (RD) (10 vs. 2, p=0.007). Pseudomonas was most commonly resistant to antibiotics, and ceftazidime (p=0.005) and cefazolin (p=0.009) resistance were higher in group 2 isolates. In group 1, five isolates were resistant to any one of the antibiotics, whereas in group 2, 13 isolates were resistant to any one of the antibiotics (p=0.024). CONCLUSIONS: In the current study, eyes in the group of endophthalmitis caused by CNSE achieved better visual acuities at the last follow-up compared to eyes with endophthalmitis caused by other bacteria. Antibiotic resistance in isolates other than CNSE is a cause of concern.

Retcam fluorescein gonioangiography: a new modality for early detection of angle neovascularization in diabetic retinopathy.

PURPOSE: To evaluate the role of Retcam fluorescein gonioangiography in detecting neovascularization of the angle and correlate the same with gonioscopy in diabetic retinopathy. METHODS: One hundred and fifty eyes of 150 patients (25 each of mild, moderate, severe, very severe nonproliferative diabetic retinopathy (NPDR) proliferative diabetic retinopathy (PDR); and PDR with high-risk characteristics) were recruited. They underwent complete ocular examination including applanation tonometry, gonioscopy, Retcam fluorescein gonioangiography, and fundus fluorescein angiography. RESULTS: Using Retcam fluorescein gonioangiography, of 150 eyes neovascularization of the angle was detected in 37 eyes (24.66%) compared with 22 eyes (14.66%) on gonioscopy (P = 0.04). Small newly formed vessels were evident only with Retcam fluorescein gonioangiography. In 10 of 50 patients (20%) with severe/very severe NPDR, angle neovascularization was appreciable on Retcam fluorescein angiography compared with 5 patients (10%) on gonioscopy. Similarly, 25 of 50 patients (50%) with PDR/PDR with high-risk characteristics had neovascularization of the angle on Retcam gonioangiography compared with 17 (34%) on gonioscopy. CONCLUSION: Retcam fluorescein gonioangiography is a novel technique for early detection of angle neovascularization in diabetic retinopathy and hence preventing progression to neovascular glaucoma. The objective nature of this test helps in precise decision making compared with gonioscopy for early intervention especially in cases of pre-PDR.

Role of additional posterior barrage laser in type 1 zone 2 retinopathy of prematurity: A randomized trial.

Purpose: The efficacy of additional barrage laser posterior to ridge in advanced stage 3 or stage 4 retinopathy of prematurity (ROP) is established, but its role in early stages is not defined. The objective was to study the efficacy of additional posterior barrage laser in type I zone 2 disease. Methods: In a randomized trial, patients with type I zone 2 ROP were recruited between February 2016 and May 2017. One eye of each baby was randomized into study and control groups, respectively. Laser photocoagulation anterior to ridge was given in the control group, and additional posterior barrage laser was performed in the study group. The outcome measures were time to complete ridge regression and final cycloplegic refraction at 3 months post-laser. Results: Forty patients (40 eyes per group) completed the required follow-up. The mean birth weight and gestational age were 1357 ± 338 g and 29.72 ± 2.57 weeks, respectively. The mean post-conceptional age during laser was 36.67 ± 3.23 weeks. The number of eyes achieving ridge regression in control and study groups was 8/40 (20%) and 27/40 (67%) at 2 weeks (P = 0.001) and 39/40 (97%) and 40/40 (100%) at 4 weeks (P = 0.4). The mean time to complete ridge regression was 3.74 ± 1.17 weeks and 2.62 ± 0.91 weeks in control and study groups, respectively (P < 0.001). The mean spherical equivalent at 12 weeks in control and study groups was -1.9 ± 2.3 Diopters and -2.4 ± 2.6 Diopters, respectively (P = 0.41). Conclusions: Additional posterior barrage laser leads to significantly faster regression of type 1 zone 2 ROP without increasing induced myopia and thereby might be a useful adjunct to conventional treatment in selected cases. Trial registration number: CTRI/2018/05/013779.

Role of fluorescein angiography guided laser treatment in aggressive retinopathy of prematurity.

PURPOSE: To compare disease regression in cases of Fluorescein Angiography (FA) guided laser vs. conventional laser treatment in infants with Aggressive retinopathy of prematurity (AROP). METHODS: 60 eyes of 30 infants of AROP were randomized into two groups. In both the group's FA was done once. Montage of the fundus, FA images was created and the vascular area, avascular areas, and skip areas after laser treatment were demarcated and measured. In group 1, FA-guided laser treatment was done whereas in group 2 they were lasered without seeing FA. Infants were followed up every week to look for skip areas and disease regression. RESULTS: The mean vascular retinal area in group 1 and group 2 on fundus images was 302.7 sq. mm and 245.8 sq. mm respectively, while the same on FA was 285.2 sq. mm and 221.3 sq. mm respectively, suggesting overestimation of the vascular area on fundus imaging compared to FA which enabled more objective estimation of avascular loop areas. Retinal skip areas in group 1 and group 2 after 1st laser were 18.7 sq. mm and 73.1 sq. mm respectively (P = 0.001), after 2nd laser was 3.7 sq. mm and 19.2 sq. mm (P = 0.003), which suggests FA-guided laser led to significantly fewer skip areas. Infants had regression in 4.1 ± 0.3 wks and 4.2 ± 0.4 wks in groups 1 and 2, respectively. CONCLUSION: FA-guided laser ensured lesser skip areas and more complete laser treatment, though regression was similar in both groups.

A Novel Method to Improve Inter-Clinician Variation in the Diagnosis of Retinopathy of Prematurity Using Machine Learning.

PURPOSE: Inter-clinician variation could cause uncertainty in disease management. This is reported to be high in Retinopathy of Prematurity (ROP), a potentially blinding retinal disease affecting premature infants. Machine learning has the potential to quantify the differences in decision-making between ROP specialists and trainees and may improve the accuracy of diagnosis. METHODS: An anonymized survey of ROP images was administered to the expert(s) and the trainee(s) using a study-designed user interface. The results were analyzed for repeatability as well as to identify the level of agreement in the classification. "Ground truth" was prepared for each individual and a unique classifier was built for each individual using the same. The classifier allowed the identification of the most important features used by each individual. RESULTS: Correlation and disagreement between the expert and the trainees were visualized using the Dipstick™ diagram. Intra-clinician repeatability and reclassification statistics were assessed for all. The repeatability was 88.4% and 86.2% for two trainees and 92.1% for the expert, respectively. Commonly used features differed for the expert and the trainees and accounted for the variability. CONCLUSION: This novel, automated algorithm quantifies the differences using machine learning techniques. This will help audit the training process by objectively measuring differences between experts and trainees. TRANSLATIONAL RELEVANCE: Training for image-based ROP diagnosis can be more objectively performed using this novel, machine learning-based automated image analyzer and classifier.

Cataract in retinopathy of prematurity - A review.

Preterm babies with retinopathy of prematurity (ROP) can become blind if they do not receive appropriate timely intervention. The presence of cataract in these individuals in addition to visual deprivation amblyopia, also delays proper screening, adequate treatment, and makes follow-up assessment difficult. Anatomical differences in these infants and amblyopia management, especially in unilateral cataract, are other important concerns, and hence, management of these cases with cataract and ROP is challenging. In this review, studies where ROP cases were associated with cataract, were evaluated with a focus on preterm individuals less than 6 months age. Preterm babies are at increased risk of developing cataract because of systemic factors. In addition, those with ROP may have cataract associated with retinal detachment or treatment received. The type of cataract, risk factors, and pathophysiology associated with each cause varies. This review highlights these different aspects of cataract in ROP including causes, pathophysiology, types of cataracts, and management. The management of these cases is critical in terms of the timing of cataract surgery and the challenges associated with surgery and posterior segment management for ROP. Anatomical differences, preoperative retina status, pupillary dilatation, neovascularization of iris in aggressive posterior ROP, fundus examination, amblyopia, and follow-up are various important aspects in the management of the same. The preoperative workup, intraoperative challenges, postoperative care, and rehabilitation in these individuals are discussed.

Preferred practice guidelines for retinopathy of prematurity screening during the COVID-19 pandemic.

Retinopathy of prematurity (ROP) is the leading cause of preventable infant blindness in the world and predominantly affects babies who are born low birth weight and premature. India has the largest number of surviving preterm births born annually. ROP blindness can be largely prevented if there is a robust screening program which detects treatment requiring disease in time. ROP treatment must be provided within 48 h of reaching this threshold of treatment making it a relative emergency. During the severe acute respiratory syndrome-coronavirus disease 2019 pandemic in 2020 ROP screening was disrupted throughout the world due to lockdowns and restriction of movement of these infants, their families, specialists and healthcare workers. The Indian ROP Society issued guidelines for ROP screening and treatment in March 2020, which was aimed at preserving the chain-of-care despite the potential limitations and hazards during the (ongoing) pandemic. This preferred practice guideline is summarized in this manuscript.

Aggressive posterior retinopathy of prematurity: a review on current understanding.

A review of literature was performed, focused on the etiopathogenesis of aggressive posterior retinopathy of prematurity (APROP), the characteristic and atypical clinical features, management strategies, anatomical and visual outcomes. Characteristically APROP has zone I/posterior zone II involvement with prominent plus disease, featureless junction, large vascular loops, flat extra-retinal fibrovascular proliferation, and a rapidly progressive course. The risk factors for APROP are extreme prematurity (birth weight ≤1000 gram and/or gestational age ≤28 weeks), dysregulated oxygen supplementation, intrauterine growth retardation, sepsis, and thrombocytopenia. The uncommon presentations include small zone I disease, a hybrid disease with additional ridge tissue, and APROP in bigger babies with birth weight greater than 1500 g. Laser photocoagulation role is limited by the resultant visual field loss and high refractive error. Although anti-vascular endothelial growth factor injection allows peripheral retinal vascularization; reactivation of disease, systemic absorption of the drug and long-term safety are the chief concerns. Early vitrectomy is required when tractional retinal detachment develops. The visual outcome depends upon the morphology and vascular development of the macula. With the limited yet emerging new understanding of the pathophysiology, a multifaceted rational and individualized treatment strategy is suggested for APROP. Best practices in neonatal intensive care may prevent the occurrence of APROP. Further studies need to be performed for the prevention and safe, effective management of APROP.

'NOPAIN-ROP' trial: Intravenous fentanyl and intravenous ketamine for pain relief during laser photocoagulation for retinopathy of prematurity (ROP) in preterm infants: A randomised trial.

OBJECTIVES: To investigate if intravenous fentanyl or intravenous ketamine can provide adequate analgesia in preterm infants undergoing laser photocoagulation for retinopathy of prematurity (ROP). DESIGN: Open-label randomised trial. SETTING: Tertiary care institution. PARTICIPANTS: Preterm infants who underwent laser photocoagulation for ROP. INTERVENTIONS: Infants were randomised to receive fentanyl as intravenous bolus dose of 2 µg/kg, followed by an intravenous infusion of 1 µg/kg/hour increased to a maximum of 3 µg/kg/hour or intravenous ketamine as bolus dose of 0.5 mg/kg, followed by further intermittent intravenous bolus doses of 0.5 mg/kg to a maximum of 2 mg/kg in the initial phase and intravenous fentanyl (bolus of 2 µg/kg followed by infusion of 2 µg/kg/hour to a maximum of 5 µg/kg/hour) or intravenous ketamine (bolus dose of 1 mg/kg followed by intermittent bolus doses of 0.5 mg/kg to a maximum of 4 mg/kg) in the revised regimen phase. MAIN OUTCOME MEASURES: Proportion of infants with adequate analgesia defined as the presence of both: (1) all the Premature Infant Pain Profile-Revised scores measured every 15 min less than seven and (2) proportion of the procedure time the infant spent crying less than 5%.Secondary outcomes included apnoea, cardiorespiratory or haemodynamic instability, feed intolerance and urinary retention requiring catheterisation during and within 24 hours following the procedure. RESULTS: A total of 97 infants were randomised (fentanyl=51, ketamine=46). The proportions of infants with adequate analgesia were 16.3% (95% CI 8.5% to 29%) with fentanyl and 4.5% (95% CI 1.3% to 15.1%) with ketamine. Ten infants (19.6%) in the fentanyl group and seven infants (15.2%) in the ketamine group had one or more side effects. In view of inadequate analgesia with both the regimens, the study steering committee recommended using a higher dose of intravenous fentanyl and intravenous ketamine. Consequently, we enrolled 27 infants (fentanyl=13, ketamine=14). With revised regimens, the proportions of infants with adequate analgesia were higher: 23.1% (95% CI 8.2% to 50.2%) with fentanyl and 7.1% (95% CI 1.3% to 31.5%) with ketamine. However, higher proportions of infants developed apnoea (n=4; 30.7%), need for supplemental oxygen (n=5, 38.4%) and change in cardiorespiratory scores (n=7; 53.8%) with fentanyl but none with ketamine. CONCLUSIONS: Fentanyl-based and ketamine-based drug regimens provided adequate analgesia only in a minority of infants undergoing laser photocoagulation for ROP. More research is needed to find safe and effective regimens that can be employed in resource constrained settings. TRIAL REGISTRATION NUMBER: CTRI/2018/03/012878.

Diagnostic Accuracy of WINROP, CHOP-ROP and ROPScore in Detecting Type 1 Retinopathy of Prematurity.

BACKGROUND: Algorithms for predicting retinopathy of prematurity (ROP) requiring treatment need to be validated in Indian settings to determine if the burden of screening can be reduced without compromising the sensitivity of existing gestation and weight-based cut offs. OBJECTIVE: To evaluate the performance of the available algorithms namely, WINROP (Weight, Insulin-like growth factor I, Neonatal ROP), CHOP-ROP (Children's Hospital of Philadelphia ROP) and ROPScore in predicting type 1 ROP and time from alarm to treatment by each algorithm. STUDY DESIGN: Ambispective observational. SETTING: Tertiary care neonatal intensive care unit in India. PARTICIPANTS: Neonates less than 32 weeks or less than 1500 g born between July, 2013 to June, 2019 (N=578), who underwent ROP screening. PRIMARY OUTCOME: Sensitivity, specificity and time from alarm to treatment by each algorithm. RESULTS: The sensitivity and specificity of WINROP was 85% and 36%, for CHOP-ROP it was 54% and 71%, and for ROPScore it was 73% and 67%, respectively in detecting type 1 ROP. A total of 50/51 (98%) of neonates with type 1 ROP underwent treatment at median gestation of 9 weeks and median time from alarm to treatment by WINROP, CHOP-ROP and ROPScore was 7, 7 and 3 weeks, respectively. CONCLUSION: WINROP, CHOP-ROP and ROPScore were not sensitive enough to replace the gestational age, weight and risk factor-based screening criteria for type 1 ROP.

Multimodal imaging of eyes with metamorphopsia after vitrectomy for rhegmatogenous retinal detachment.

PURPOSE: To assess the retinal features in eyes with postoperative metamorphopsia (POM) following rhegmatogenous retinal detachment (RRD) repair using multimodal imaging (MMI). METHODS: In this cross-sectional; case-control study, patients after successful RRD repair following 25-gauge vitrectomy, clear vitreous cavity, and corrected distance visual acuity (CDVA)>20/200 were categorized using Amsler chart: cases with POM and controls without POM. MMI was performed on swept-source platform (Triton, Topcon Inc) and the confocal scanning laser ophthalmoscope system (Spectralis HRA, Heidelberg). The measures assessed were CDVA, morphological features on optical coherence tomography, autofluorescence, and multicolor imaging (MCI). RESULTS: Thirty-nine eyes were included in each group. Cases had greater number of eyes with total RRD (P = 0.029) preoperatively; abnormal foveal contour (P = 0.036), ellipsoid zone (EZ) disruption (P < 0.001) and poorer postoperative CDVA (P = 0.046) as compared to controls. Outer retinal folds and retinal shift (unintentional translocation of retina after reattachment surgery for RRD) did not differ significantly between the groups (P = 0.48 and 0.35, respectively). On MCI, the distribution of detected ERM was similar between the groups (P = 0.25). Postoperative CDVA was significantly worse in eyes with POM. CONCLUSION: POM is affected by extent of RRD, postoperative foveal contour, and EZ status but not by retinal shift.